Drug chirality in anesthesia.

MORE than one-third of all synthetic drugs are chiral and are marketed as racemates, 1:1 mixtures of two types of molecules bearing identical chemical constitution and atomic connections but with a different spatial orientation of their constituent atoms. Drug receptors may discriminate between stereoisomers in several ways; binding may favor one form over the other, and to a degree varying with the drug molecule and with the state of the receptor, or stereoisomers may have opposite effects, one form being an agonist at the same receptor where its mirror image is antagonist. Stereoselectivity is interesting from both a scientific and clinical point of view. Scientifically, stereoselective responses give evidence for specific receptor-mediated responses and information about the structure of the binding site. Clinically, the use of single stereoisomers of chiral anesthetic drugs has received increasing attention recently, because it might decrease side effects and increase drug-safety. In this brief review we define some fundamental terms of stereochemistry, introduce the nomenclature for designating the different stereoisomers (enantiomers), present general principles of stereoselective drug action, and describe the possible contributions of pharmacokinetic and pharmacodynamic mechanisms to stereoselective advantages. Finally, three examples of chiral anesthetic drugs are discussed in the above context.